Brominated Diphenyl Ether Congeners Research Articles

Immunomodulatory effects of Brominated Flame Retardants on Cytokine Production in Mast cells

Polybrominated diphenyl ethers (PBDEs), extensively used as flame-retardants have been classified as persistent environmental pollutants. PBDEs have also been shown to cause neurotoxicity, immunotoxicity, and endocrine disruption; however, the exact mechanisms are largely unknown. In this study, we propose to investigate PBDE-induced immunotoxicity in mast cells. We examined the effects of two of the most commonly occurring brominated diphenyl ether (BDE) congeners, BDE-47 and -99, and a metabolite of BDE-47, 6-OH-BDE-47 on MC/9 mast cells. MC/9 cells treated with BDE-47, -99, and 6-OH-BDE-47 (0.25, 0.5, 5, 20 and 40μM, 24h) were stimulated with IgE/antigen (1μg/ml), and levels of IL-6 and TNF-α were measured by ELISA. Our results indicate that PBDEs inhibit the IgE-mediated cytokine release in MC/9 cells in a concentration-dependent manner. Interestingly, exposure to BDE-47 and 6-OH-BDE47 decreased IL-6 release in a concentration-dependent manner; however, BDE-99 decreased IL-6 release only at concentrations above 20 μM. These results demonstrate that tetra-brominated BDE-47 and its 6-OH metabolite can suppress cytokine release with increasing concentrations, while penta-brominated BDE-99 congener inhibits IL-6 release only at higher concentrations. We observed a similar decrease in TNF-α release when tge MC/9 cells were exposed to the BDE-47, -99, and 6-OH-BDE-47. Mast cell degranulation measured by β-hexoaminidase also showed that BDE congeners decreased degranulation in a concentration-dependent manner in IgE stimulated mast cells. In order to test effects on cell viability, we exposed the MC/9 cells to increasing concentrations of the BDE congeners and measured cytotoxicity at 24 and 48h by MTS assay. We found that tetra-brominated BDE-47 exhibited more potent cytotoxicity (EC50 µM =42.38 at 24h and 32.33 at 48h) in comparison to the penta-brominated BDE-99 (EC50 µM =48.41 and 35.04 at 48h) in the MC/9 cells. However, the 6-OH metabolite of BDE-47 was more cytotoxic in comparison to its parent compound BDE-47 as well as penta-brominated BDE-99 (EC50 µM =25.82 at 24h and 20.16 at 48h). We are further characterizing the development of apoptosis in the MC9 cells in the presence of BDE congeners. Our results suggest that PBDE congeners can modulate cytokine release in mast cells, and the extent of inhibition is dependent on the bromination of PBDEs. These results address the need to better understand the molecular and cellular mechanisms by which PBDE exposure can mediate immunotoxicity.

Unraveling the Relationship between the Concentrations of Hydrophobic Organic Contaminants in Freshwater Fish of Different Trophic Levels and Water Using Passive Sampling.

The concentrations of hydrophobic organic compounds (HOCs) in aquatic biota are used for compliance, as well as time and spatial trend monitoring in the aqueous environment (European Union water framework directive, OSPAR). Because of trophic magnification in the food chain, the thermodynamic levels of HOCs, for example, polychlorinated biphenyl congeners, dichlorodiphenyltrichloroethane, and brominated diphenyl ether congeners, in higher trophic level (TL) organisms are expected to be strongly elevated above those in water. This work compares lipid-based concentrations at equilibrium with the water phase derived from aqueous passive sampling (CL⇌water) with the lipid-based concentrations in fillet and liver of fish (CL) at different TLs for three water bodies in the Czech Republic and Slovakia. The CL values of HOCs in fish were near CL⇌water, only after trophic magnification up to TL = 4. For fish at lower TL, CL progressively decreased relative to CL⇌water as KOW of HOCs increased above 106. The CL value decreasing toward the bottom of the food chain suggests nonequilibrium for primary producers (algae), which is in agreement with modeling passive HOC uptake by algae. Because trophic magnification and the resulting CL in fish exhibit large natural variability, CL⇌water is a viable alternative for monitoring HOCs using fish, showing a twofold lower confidence range and requiring less samples.

Brominated Flame Retardants alter Cytokine Production in Mast Cells

Polybrominated diphenyl ethers (PBDEs), extensively used as flame‐retardants have been classified as persistent environmental pollutants. PBDEs have also been shown to cause neurotoxicity, immunotoxicity and endocrine disruption; however, the exact mechanisms are largely unknown. In this study, we propose to investigate PBDE‐induced immunotoxicity in mast cells. We examined the effects of two of the most commonly occurring brominated diphenyl ether (BDE) congeners, BDE‐47 and −99, and a metabolite of BDE‐47, 6‐OH‐BDE‐47 on MC/9 mast cells. MC/9 cells treated with BDE‐47, −99 and 6‐OH‐BDE‐47 (0.25, 0.5, 5, 20 and 40μM, 24h) were stimulated with IgE/antigen (1μg/ml), and levels of IL‐6 and TNF‐α were measured by ELISA. Our results indicate that PBDEs inhibit the IgE‐mediated cytokine release in MC/9 cells in a concentration‐dependent manner. Interestingly, exposure to BDE‐47 and 6‐OH‐BDE47 decreased IL‐6 release in a concentration‐dependent manner; however, BDE‐99 decreased IL‐6 release only at concentrations above 20 μM. These results demonstrate that tetra‐brominated BDE‐47 and its 6‐OH metabolite can suppress cytokine release with increasing concentrations, while penta‐brominated BDE‐99 congener inhibits IL‐6 release only at higher concentrations. Mast cell degranulation measured by β‐hexoaminidase also showed that BDE congeners decreased degranulation in a concentration‐dependent manner in IgE stimulated mast cells. In order to test effects on cell viability, we exposed the MC/9 cells to increasing concentrations of the BDE congeners and measured cytotoxicity at 24 and 48h by MTS assay. We found that tetra‐brominated BDE‐47 exhibited more potent cytotoxicity (EC50 μM =42.38 at 24h and 32.33 at 48h) in comparison to the penta‐brominated BDE‐99 (EC50 μM =48.41 and 35.04 at 48h) in the MC/9 cells. However, the 6‐OH metabolite of BDE‐47 was more cytotoxic in comparison to its parent compound BDE‐47 as well as penta‐brominated BDE‐99 (EC50 μM =25.82 at 24h and 20.16 at 48h). We are further characterizing development of apoptosis in the MC9 cells in the presence of BDE congeners. Our results suggest that PBDE congeners can modulate cytokine release in mast cells and the extent of inhibition is dependent on the bromination of PBDEs. These results address the need to better understand the molecular and cellular mechanisms by which PBDE exposure can mediate immunotoxicity.

A Human Mixture Risk Assessment for Neurodevelopmental Toxicity Associated with Polybrominated Diphenyl Ethers Used as Flame Retardants.

Background:The European Food Safety Authority recently concluded that the exposure of small children (1–3 y old) to brominated diphenyl ether (BDE)-99 may exceed acceptable levels defined in relation to neurodevelopmental toxicity in rodents. The flame retardant BDE-209 may release BDE-99 and other lower brominated BDEs through biotic and abiotic degradation, and all age groups are exposed not only to BDE-209 and -99 but also to a cocktail of BDE congeners with evidence of neurodevelopmental toxicity. The possible risks from combined exposures to these substances have not been evaluated.Objectives:We performed a congener-specific mixture risk assessment (MRA) of human exposure to combinations of BDE-209 and other BDEs based on estimated exposures via diet and dust intake and on measured levels in biologic samples.Methods:We employed the Hazard Index (HI) method by using BDE congener-specific reference doses for neurodevelopmental toxicity.Results:Our HI analysis suggests that combined exposures to polybrominated diphenyl ethers (PBDEs) may exceed acceptable levels in breastfeeding infants (0–3 mo old) and in small children (1–3 y old), even for moderate (vs. high) exposure scenarios. Our estimates also suggest that acceptable levels of combined PBDEs may be exceeded in adults whose diets are high in fish. Small children had the highest combined exposures, with some estimated body burdens that were similar to body burdens associated with developmental neurotoxicity in rodents.Conclusions:Our estimates corroborate reports from several recent epidemiological studies of associations between PBDE exposures and neurobehavioral outcomes, and they support the inclusion of BDE-209 in the persistent organic pollutant (POP) convention as well as the need for strategies to reduce exposures to PBDE mixtures, including maximum residue limits for PBDEs in food and measures for limiting the release of PBDEs from consumer waste. https://doi.org/10.1289/EHP826

Excited States and photodebromination of selected polybrominated diphenyl ethers: computational and quantitative structure--property relationship studies.

This paper presents a density functional theory (DFT)/time-dependent DFT (TD-DFT) study on the lowest lying singlet and triplet excited states of 20 selected polybrominateddiphenyl ether (PBDE) congeners, with the solvation effect included in the calculations using the polarized continuum model (PCM). The results obtained showed that for most of the brominated diphenyl ether (BDE) congeners, the lowest singlet excited state was initiated by the electron transfer from HOMO to LUMO, involving a π–σ* excitation. In triplet excited states, structure of the BDE congeners differed notably from that of the BDE ground states with one of the specific C–Br bonds bending off the aromatic plane. In addition, the partial least squares regression (PLSR), principal component analysis-multiple linear regression analysis (PCA-MLR), and back propagation artificial neural network (BP-ANN) approaches were employed for a quantitative structure-property relationship (QSPR) study. Based on the previously reported kinetic data for the debromination by ultraviolet (UV) and sunlight, obtained QSPR models exhibited a reasonable evaluation of the photodebromination reactivity even when the BDE congeners had same degree of bromination, albeit different patterns of bromination.

BDE99 (2,2′,4,4′,5-pentabromodiphenyl ether) suppresses differentiation into neurotransmitter phenotypes in PC12 cells

Early-life exposures to brominated diphenyl ethers (BDEs) lead to neurobehavioral abnormalities later in life. Although these agents are thyroid disruptors, it is not clear whether this mechanism alone accounts for the adverse effects. We evaluated the impact of 2,2′,4,4′,5-pentabromodiphenyl ether (BDE99) on PC12 cells undergoing neurodifferentiation, contrasting the effects with chlorpyrifos, a known developmental neurotoxicant. BDE99 elicited decrements in the number of cells, evidenced by a reduction in DNA levels, to a lesser extent than did chlorpyrifos. This did not reflect cytotoxicity from oxidative stress, since cell enlargement, monitored by the total protein/DNA ratio, was not only unimpaired by BDE99, but was actually enhanced. Importantly, BDE99 impaired neurodifferentiation into both the dopamine and acetylcholine neurotransmitter phenotypes. The cholinergic phenotype was affected to a greater extent, so that neurotransmitter fate was diverted away from acetylcholine and toward dopamine. Chlorpyrifos produced the same imbalance, but through a different underlying mechanism, promoting dopaminergic development at the expense of cholinergic development. In our earlier work, we did not find these effects with BDE47, a BDE that has greater endocrine disrupting and cytotoxic effects than BDE99. Thus, our results point to interference with neurodifferentiation by specific BDE congeners, distinct from cytotoxic or endocrine mechanisms.

Cyto-genotoxic effects induced by three brominated diphenyl ether congeners on the freshwater mussel Dreissena polymorpha

Polybrominated diphenyl ethers (PBDEs) are a group of highly hydrophobic and persistent chemicals that has been used as flame retardants in several industrial applications. They have been detected in various environmental matrices worldwide and an increasing number of studies have recently been carried out to investigate their potential toxicity on ecosystem communities. Although a variety of biological damage has been documented in vertebrates, the effects on invertebrates are largely unknown. The objective of the present study was to determine the cyto-genotoxic effects induced by single exposure to three concentrations of 2,4,2′,4′-tetra BDE (BDE 47), 2,2′,4,4′,6-penta BDE (BDE-100) and 2,2′,4,4′,5,6′-hexa BDE (BDE-154) on the freshwater mussel Dreissena polymorpha by a multi-biomarker approach. We performed on bivalve hemocytes the Single Cell Gel Electrophoresis (SCGE) assay, the DNA Diffusion assay and the Micronucleus test (MN test) to assess genotoxicity, while the Neutral Red Retention Assay (NRRA) was used to evaluate cytotoxic effects. Results showed that BDE-47 did not produce any genetic damage at the tested concentrations (0.1μg/L, 0.5μg/L and 1μg/L), while BDE-100 and BDE-154 can be considered moderately genotoxic, since both primary and fixed DNA injuries were induced. The NRRA indicated a moderate increase in cellular stress in BDEs-treated bivalves. Thus, our data seems to suggest that investigated BDEs may pose a low risk to freshwater mussels at environmental concentrations.

Concentrations and speciation of polybrominated diphenyl ethers in human amniotic fluid

Polybrominated diphenyl ethers (PBDEs) are persistent organic chemicals used as flame retardants in textiles, plastics, and consumer products. Although PBDE accumulation in humans has been noted since the 1970s, few studies have investigated PBDEs within the gestational compartment, and none to date has identified levels in amniotic fluid. The present study reports congener-specific brominated diphenyl ether (BDE) concentrations in second-trimester clinical amniotic fluid samples collected in 2009 from fifteen women in southeast Michigan, USA. Twenty-one BDE congeners were measured by GC/MS/NCI. The average total PBDE concentration was 3795pg/ml amniotic fluid (range: 337–21,842pg/ml). BDE-47 and BDE-99 were identified in all samples. Based on median concentrations, the dominant congeners were BDE-208, 209, 203, 206, 207, and 47 representing 23, 16, 12, 10, 9 and 6%, respectively, of the total detected PBDEs. PBDE concentrations were identified in all amniotic fluid samples from southeast Michigan, supporting a need for further investigations of fetal exposure pathways and potential impacts on perinatal health.

Does Flying Present a Threat of Polybrominated Diphenyl Ether Exposure?

To investigate possible exposure to polybrominated diphenyl ethers (PBDEs) in US professional airline workers. We recruited 30 healthy US professional airline workers who lived in the Dallas, Texas, area to test their blood PBDE levels. We examined the relationship between hours worked in an airplane and total PBDE blood levels. Total PBDE blood levels from the 30 volunteers were unremarkable despite minor elevations of certain congeners in a few volunteers. No statistically significant correlations were noted between hours in airplanes in the past 1 or 5 years and levels of individual brominated diphenyl ethers congeners or total PBDEs. We hypothesized that elevated PBDE levels in commercial aviation workers could be found associated with time spent in airliners. Our findings do not support such an association.

Evaluation of the state-of-the-art measurement capabilities for selected PBDEs and decaBB in plastic by the international intercomparison CCQM-P114

An international intercomparison involving eight national metrology institutes (NMIs) was conducted to establish their current measurement capabilities for determining five selected congeners from the brominated flame retardant classes polybrominated diphenyl ethers and polybrominated biphenyls. A candidate reference material consisting of polypropylene fortified with technical mixtures of penta-, octa- and decabromo diphenyl ether and decabromo biphenyl, which was thoroughly assessed for material homogeneity and stability, was used as study material. The analytical procedures applied by the participants differed with regard to sample pre-treatment, extraction, clean-up, employed calibrants and type of calibration procedure as well as regarding analytical methods used for separation, identification and quantification of the flame retardant congeners (gas chromatography coupled to an electron capture detector (GC-ECD), gas chromatography-mass spectrometry in the electron ionisation mode (GC-EI-MS), gas chromatography-mass spectrometry in the electron capture negative ionisation mode (GC-ECNI-MS), and liquid chromatography-inductive coupled plasma-mass spectrometry (LC-ICP-MS)). The laboratory means agreed well with relative standard deviations of the mean of means of 1.9%, 4.8%, 5.5% and 5.4% for brominated diphenyl ether (BDE) 47, 183 and 209 and for the brominated biphenyl (BB) congener 209, respectively. For BDE 206, a relative standard deviation of 28.5% was obtained. For all five congeners, within-laboratory relative standard deviations of six measurements obtained under intermediate precision conditions were between 1% and 10%, and reported expanded measurements uncertainties typically ranged from 4% to 10% (8% to 14% for BDE 206). Furthermore, the results are in good agreement with those obtained in the characterization exercise for determining certified values for the flame retardant congeners in the same material. The results demonstrate the state-of-the-art measurement capabilities of NMIs for quantifying representative BDE congeners and BB 209 in a polymer. The outcome of this intercomparison (pilot study) in conjunction with possible improvements for employing exclusively calibrants with thoroughly assessed purity suggests that a key comparison aiming at underpinning calibration and measurement capability (CMC) claims of NMIs can be conducted.

Comparative Cytotoxicity and Intracellular Accumulation of Five Polybrominated Diphenyl Ether Congeners in Mouse Cerebellar Granule Neurons

Polybrominated diphenyl ethers (PBDEs), a group of flame retardants comprising 209 congeners, have become widespread environmental pollutants. High levels of PBDEs have been detected in human tissues, particularly in North America, and body burden is especially high in infants and toddlers because of exposure through breast milk and house dust. Increasing evidence, provided by animal studies, suggests that PBDEs are developmental neurotoxicants, although the underlying mechanisms are still unknown. Various PBDEs have been reported to cause oxidative stress and to induce apoptotic cell death in several cell types. In the present study, we investigated the comparative neurotoxicity in mouse cerebellar granule neurons of five brominated diphenyl ether (BDE) congeners, chosen among the most commonly found at the highest levels in human tissues. All BDE congener tested (BDE-47, BDE-99, BDE-100, BDE-153, and BDE-209) decreased cell viability and induced apoptotic cell death, which was prevented by antioxidants. They also caused oxidative stress, as indicated by an increase in reactive oxygen species and in lipid peroxidation. For all end points measured, the potency ranking of the congeners was BDE-100 > BDE-47 > BDE-99 > BDE-153 >> BDE-209. Measurement of BDE congener levels in neurons after exposure to different concentrations showed a significant accumulation in cells, which followed the same relative ranking. The findings suggest that all BDE congeners tested exhibit the same general mode of action (induction of oxidative stress-mediated apoptosis) and that the ability of each isomer to elicit such effects is dependent upon their accumulation in neurons, particularly in the microsomal fraction and the mitochondria.

Relationships Between Brominated Flame Retardant Concentrations in House Dust and Serum Hormone Levels in Men

ISEE-0454 Background and Objective: Human exposure to brominated flame retardants (BFRs) is widespread, occurring primarily through diet or contact with indoor dust. There is laboratory evidence of endocrine disruption in animals following exposure to BFRs, but human studies are limited. In this preliminary investigation, we examined the association between BFR levels in house dust and hormone levels in men. Methods: We measured serum hormone levels and BFR concentrations in participant vacuum bag dust from 38 men recruited through a Massachusetts infertility clinic as part of an ongoing study of environmental exposures and male reproductive health. Statistical methods included the calculation of Spearman correlations among BFRs and between BFRs and serum hormone levels, and multivariable linear regression. Results: There were strong correlations (r ≥ 0.80, P < 0.05) among dust concentrations of brominated diphenyl ether (BDE) congener groups with a similar degree of bromination. Positive correlations were found (P ≤ 0.05) between several BDE congeners and serum levels of prolactin and total T3, and between bistribromophenoxyethane and total T3. Hexabromocyclododecane was positively correlated with free androgen index (FAI) (r = 0.46, P = 0.004). Most of these relationships remained statistically significant or suggestive in multivariate linear regression models adjusted for age and BMI. There was a suggestive inverse association between BDE209 and testosterone when adjusting for age, BMI, and serum sex hormone binding globulin (SHBG) (P = 0.09). When dust concentrations of BDE99 were combined with results from a previous analysis of 24 men from the same cohort (n = 62), regression models adjusted for age, BMI, and dust analytical method showed positive relationships between BDE99 and serum estradiol, free T4, and SHBG (P < 0.05). Inverse associations between BDE99 and follicle stimulating hormone (P < 0.05) and FAI (P = 0.11) were also found. Conclusion: This study provides evidence of altered hormone levels in relation to BFR exposure and that house dust may be an important source of human BFR exposure.

Anaerobic transformation of a technical pentabromo diphenyl ether product using superreduced vitamin B12

Technical pentabromo diphenyl ether (DE-71) was anaerobically transformed using superreduced cyanocobalamin (vitamin B12). The principal pathway was identified to be reductive debromination. As a consequence, the proportion of higher brominated homologues decreased in favor of the lower brominated diphenyl ethers (BDEs) while the molar amount of BDE congeners was virtually constant throughout the experiment. As an example, the ratios of BDE 99/BDE 47 was >1 at the start, ∼1 after 1 week, and <1 after 2 weeks. A further feature identified was the alternating removal of bromine atoms from the two rings when two or more Br were substituted by hydrogen. BDE 49 and BDE 66 proved to be good indicators for the reductive debromination of both DE-71 and DE-79. Hence, a thorough study of BDE 49 and BDE 66 might be helpful to solve the question whether high amounts of key-PBDEs in technical pentabromo diphenyl ether in the environment originate from such sources or are debromination products of higher BDEs.

Fate of polybrominated diphenyl ethers in the environment of the Pearl River Estuary, South China

Ninety-six riverine runoff samples collected at eight major outlets in the Pearl River Delta (PRD), South China, during 2005–2006 were analyzed for 17 brominated diphenyl ether (BDE) congeners (defined as Σ 17PBDE). Fourteen and 15 congeners were detected, respectively, in the dissolved and particulate phases. These data were further used to elucidate the partitioning behavior of BDE congeners in riverine runoff. Several related fate processes, i.e. air–water exchange, dry and wet deposition, degradation, and sedimentation, within the Pearl River Estuary (PRE), were examined to estimate the inputs of Σ 10PBDE (sum of the target BDE congeners, BDE-28, -47, -66, -85, -99, -100, -138, -153, -154, and -183) and BDE-209 from the PRD to the coastal ocean based on mass balance considerations. The results showed that annual outflows of Σ 10PBDE and BDE-209 were estimated at 126 and 940 kg/year, respectively from the PRE to coastal ocean. Besides sedimentation and degradation, the majority of Σ 10PBDE and BDE-209 discharged into the PRE via riverine runoff was transported to the coastal ocean.

Effect of Tween 80 and β-cyclodextrin on degradation of decabromodiphenyl ether (BDE-209) by White Rot Fungi

The environmental safety of decabromodiphenyl ether (BDE-209), a widely used flame retardant, has been the topic of controversial discussions during the past several years. Degradation of BDE-209 into lower brominated diphenyl ether congeners, exhibiting a higher bioaccumulation potential, has been a critical issue. White rot fungi are known to degrade a wide variety of recalcitrant pollutants. In this work, white rot fungi were used to degrade BDE-209 in liquid culture medium, and the effects of Tween 80 and β-cyclodextrin on BDE-209 degradation by white rot fungi were evaluated. On the basis of these results, it appears that BDE-209 could be degraded by white rot fungi, and Tween 80 and β-cyclodextrin can both increase the biodegradation. The best result in Tween 80 experiments was obtained at a Tween 80 concentration of 500 mg l −1 within 10 d, which showed 96.5% (w/w) BDE-209 transformed. Tween 80 at a high concentration will restrain the fungal growth and the degradation of BDE-209. However, β-cyclodextrin had positive effects both on the BDE-209 degradation and the fungal growth.

Bioaccumulation and trophic transfer of some brominated flame retardants in a Lake Winnipeg (Canada) food web

The extent of bioaccumulation and trophic transfer of brominated diphenyl ether (BDE) congeners, hexabromocyclododecane (HBCD) diastereoisomers (alpha, beta, and gamma), decabromodiphenylethane (DBDPE), and bis(2,4,6-tribromophenoxy)ethane (BTBPE) was examined in a Lake Winnipeg (Canada) food web. Six species of fish, zooplankton, mussels, sediment, and water from the south basin of the lake were selected for study. Significant positive correlations were found between concentrations of total (sigma) polybrominated diphenylethers (PBDEs; p < 0.005), sigmaHBCDs (p < 0.0001), BTBPE (p < 0.0001), and lipid content in fish. Strong positive linear relationships also were observed from individual plots of BDE 47, BDE 209, and DBDPE concentrations (lipid wt) and trophic level (based on delta15N), suggesting that these compounds biomagnify in the Lake Winnipeg food web. Biomagnification factors varied for the chemicals studied. Plots of log bioaccumulation factors for mussel and zooplankton versus log octanol-water partition coefficient (Kow) were similar and suggest that neither mussels nor zooplankton are in equilibrium with the water. Fifteen BDE congeners were consistently detected in water (dissolved phase, n = 3), with BDE 47 having the greatest concentration (17 pg/L). The rank order of compounds in water (arithmetic mean +/- standard error) were sigmaPBDEs (49 +/- 12 pg/ L) > alpha-HBCD (11 +/- 2 pg/L) > BTBPE (1.9 +/- 0.6 pg/L). Concentrations of DPDPE, BDE 209, and beta- and -gamma-HBCD isomers were below their respective method detection limits (MDLs) in water. Total PBDE concentrations in sediment (n = 4) were greater than any other brominated flame retardant examined in the present study and ranged from 1,160 to 1,610 ng/g (dry wt), with BDE 209 contributing roughly 50% of the total. The gamma-HBCD isomer was detected at concentrations of 50 +/- 20 pg/g (dry wt) in sediment, whereas BTBPE and DBDPE were consistently below their respective MDLs in sediment.

Toxicokinetics of Polybrominated Diphenyl Ether Congeners 47, 99, 100, and 153 in Mice

The congener profiles of polybrominated diphenyl ethers (PBDEs) in human and wildlife samples are dominated by brominated diphenyl ether (BDE) congeners 47, 99, 100, 153, and 154, all of which are components of the commercial pentaBDE mixtures commonly used in a variety of flammable consumer products. Very little information is available on the toxicokinetics of these congeners and no studies are available directly comparing these BDE congeners in mice. Therefore, the objective of this study was to compare the distribution, metabolism, and excretion of BDEs 47, 99, 100 and 153. Female C57BL/6 mice were administered a single dose of BDE (1 mg/kg: 2.1, 1.9, 1.9, and 1.8 mumol/kg, respectively) intravenously. Excretion was monitored daily, and terminal tissue disposition was examined 5 days following exposure. All BDE congeners in this study distribute with similar patterns into lipophilic tissues; however, tissue concentrations 5 days following exposure were much higher for BDE-153 than for 100, 99, and 47, respectively. Excretion rates were inversely related to tissue concentrations as BDE-47 was the most rapidly excreted congener, followed by BDE-99, -100, and -153. Differences in tissue concentrations were largely driven by congener-specific urinary elimination rates which were associated with protein binding in the urine. While the overall rate of metabolism appeared to be low, analysis of metabolites in daily feces samples revealed that BDE-99 was the most rapidly metabolized congener in this study. The results of this study demonstrate that congener substitution plays a role in the distribution, metabolism, and excretion of PBDEs in mice and it is therefore important to consider the differential toxicokinetic parameters associated with each congener when assessing the risk to human health from these PBDE congeners.

Anaerobic transformation of a technical brominated diphenyl ether mixture by super‐reduced vitamin B12 and dicyanocobinamide

The anaerobic transformation of the technical octabromo diphenyl ether mixture, DE-79, was investigated by incubation with two super-reduced corrinoids, dicyanocobinamide and cyanocobalamin (vitamin B12). The transformation produced 33 brominated diphenyl ethers (BDEs), 23 of which could be assigned to known structures. Within 1 d, the hepta- to nona-BDEs in DE-79 were almost quantitatively transformed with dicyanocobinamide to lower-brominated homologs. Along with the decrease of high-brominated congeners, concentrations of some tetra- to hexabromo congeners initially increased, followed by a decreasing or constant concentration during longer incubations. Super-reduced cyanocobalamin also was able to transform BDE congeners of DE-79. Whereas the transformation rates of hepta- to nona-BDEs of DE-79 by both corrinoids were comparable, tri- to hexa-BDEs were susceptible to further transformation by super-reduced cyanocobalamin. Incubation of DE-79 with either corrinoid produced significant amounts of BDE 49. Because this congener is found in small quantities in both penta- and octabromo technical BDE mixtures, it may be a suitable indicator for reductive debromination of higher-brominated BDEs. Isolated BDE 196 was incubated as well with super-reduced dicyanocobalamine. After 1 d, 13 BDEs could be detected, with BDE 153, BDE 100, and BDE 99 dominating. After 7 d, only tetra-BDEs or lower-brominated BDEs were detectable. It could be shown that reductive debromination by super-reduced corrinoids is a possible source for lower-brominated BDEs (i.e., BDE 47, BDE 99, BDE 153, and BDE 154). The patterns observed with our bench-scale study design demonstrate that anaerobic transformation in the presence of reducing agents can help to explain the occurrence of environmentally relevant BDE congeners (e.g., BDE 47, BDE 99, and BDE 153).

Inhibition of metamorphosis in tadpoles of Xenopus laevis exposed to polybrominated diphenyl ethers (PBDEs)

Tadpoles of the African clawed frog, Xenopus laevis were exposed, beginning at stage 50, to a commercial pentabromodiphenyl ether mixture (DE-71) through the diet. Subsequent experiments were conducted using a single intraperitoneal injection at stage 58 with limited quantities of two purified brominated diphenyl ether (BDE) congeners, BDE47 and BDE99 and DE-71 to determine the relative potency of these BDE congeners within the commercial mixture. Significant inhibition of tail resorption, delayed metamorphosis and impacts on skin pigmentation were observed in Xenopus exposed to DE-71 in the diet at nominal doses of 1000 and 5000 μg g −1 of food. The estimated time required for 50% of the tadpoles to complete metamorphosis was significantly lengthened in Xenopus exposed to a dietary concentration of 1 μg DE-71 per gram of food. Analysis of PBDEs (sum of 32 congeners) in Xenopus from the treatment with 5000 μg g −1 of DE-71 indicated that the frogs accumulated an average of 1030 μg g −1 (wet weight) of PBDEs. In the intraperitoneal injection trials, similar inhibitory responses were observed in Xenopus injected with DE-71 at a nominal dose of 60 μg per tadpole, or injected with BDE47 at a nominal dose of 100 μg per tadpole. No responses were observed in Xenopus injected with BDE99 at doses up to 100 μg per tadpole. Complete inhibition of metamorphosis was observed only in the highest DE-71 dietary treatment. The results of this study are consistent with a mechanism of action of PBDEs involving competitive inhibition of binding of thyroid hormones to transporter proteins, although the mechanism cannot be definitively determined from this study. The observed effects may have occurred through other mechanisms, including sublethal toxicity. The doses used in this study are greater than the levels of PBDEs to which anurans are exposed in the environment, so further studies are required to determine whether exposure to PBDEs at environmentally relevant concentrations can affect frog metamorphosis.

Levels and trends of brominated flame retardants in the European environment

In this paper, we review those data which have recently become available for brominated flame retardants (particularly the brominated diphenyl ethers (BDEs) and hexabromocyclododecane (HBCD)) in samples from the European environment. Environmental compartments studied comprise the atmosphere, sediments and soils, sewage sludges, and a variety of biological samples and food chains. This is currently a very active research area, and we cite over 70 studies reported in the literature during 2003–04. Findings include that the input of BDEs (especially BDE209) to the Baltic Sea by atmospheric deposition now exceeds that of PCBs by a factor of almost 40 times. Sewage sludge samples from both industrial and background locations show concentrations of BDEs, HBCD and tetrabromobisphenol-A (TBBP-A) that are of a similar order, indicating that the major source is from diffuse leaching from products into wastewater streams from users, households and industries generally. Point-sources from industries using BFRs (e.g. the textile industry) also generate local hot-spots. Sediment core studies identified the presence of two of the three PBDE formulations. The penta-mix formulation was clearly present from the beginning of the 1970s, but the deca-mix only appeared in the late 1970s. BDE183, BDE209 and HBCD were detected in peregrine falcons from Sweden and other birds feeding on terrestrial food chains. BDEs are found widely distributed in fish, including those from high mountain lakes in Europe, as a consequence of long-range atmospheric transport and deposition. A temporal trend study in archived freeze-dried mussels from the Seine estuary, France, indicated an exponential increase in BDE concentrations during the period 1982–1993, which levelled off in 1999 and 2001 and then began to decline after 2002. HBCD was detected in liver and blubber samples from harbour seals and harbour porpoises from the Wadden and North Seas, though very few animals yielded positive values for TBBP-A. There are difficulties in comparing data on ∑BDE from studies in which different suites of BDE congeners have been determined, and we suggest a common suite which will allow the study of all three commercial PBDE formulations.